In A. thaliana, alleles of R loci confer resistance by interacting with specific avirulence (avr) gene-dependent products of bacterial or fungal pathogens. The rapid progress being made in the molecular and functional characterization of R genes provides a timely opportunity to investigate the ecological or molecular population genetics of resistance in this species: essentially nothing is known about the extent of polymorphism at R gene loci, the age of alleles, or the geographical distribution of polymorphism. We propose to investigate why many R gene loci are polymorphic for two or more functional alleles by utilizing two complementary approaches for studying selection acting on resistance loci. First, we will perform a statistical analysis of DNA sequence polymorphism within and among populations (and species) at five R loci and along two chromosomes. Second, we will experimentally estimate the relative fitness of resistant and susceptible alleles at two loci, Rpm1 and Rps5, by constructing transgenic and control lines of A thaliana. Together, these studies will allow us to test specific selection models for the maintenance of polymorphism and the evolution of R genes in A. thaliana, and will allow us to make inferences about the spatio-temporal population dynamics of these host-pathogen interactions. Our data will enable us to test the widespread belief that there will be a rapid selective turnover of R alleles resulting from an evolutionary arms race between pathogen and host. We will also test for evidence of long-term evolutionary maintenance of allelic variation at R loci, a prediction made by a subclass of theoretical models of gene-for-gene coevolution. These tests require information on background levels of polymorphism, which we will generate through a systematic survey of nucleotide polymorphisms along two chromosomes of A. thaliana. Information on the extent and spatial patterning of molecular genetic variation is integral to testing for historical evidence of selection at R loci, and will help establish Arabidopsis as a model system for molecular evolutionary studies on a wealth of plant traits.